Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Structural Hippocampal Damage Following Anti-N-Methyl-D-Aspartate Receptor Encephalitis
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DOI：
10.1016/j.biopsych.2015.02.024
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发表时间：
2016-05-01
影响因子：
10.6
通讯作者：
Paul, Friedemann
中科院分区：
文献类型：
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作者：
Finke, Carsten;Kopp, Ute A.;Paul, Friedemann
背景：大多数抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎患者存在持续性记忆障碍，尽管常规的临床磁共振成像并不明显。随着这些患者急诊护理的改善，神经认知障碍是导致长期发病率的主要因素，因此成为关注的焦点。方法：对40例急性病期后抗NMDAR脑炎患者和25名健康对照组进行多模式结构成像，将海马区体积测量与海马微结构完整性分析相结合。对所有患者的言语和视觉空间记忆能力进行评估，并进行相关和中介分析，以检验海马体结构完整性、记忆能力和疾病严重程度之间的关系。结果：患者的海马体体积显著缩小，海马子场分析显示双侧海马回路的输入和输出区萎缩。患者的双侧海马区微结构完整性受损。重要的是，海马体体积和微结构完整性测量与记忆表现、疾病严重程度和病程相关。中介分析表明，海马区微结构介导了疾病严重程度对记忆表现的影响。结论：来自接受广泛多模式磁共振成像的最大抗NMDAR脑炎患者的数据表明，海马区结构损伤和相关的记忆障碍是脑炎的重要长期后遗症。与疾病持续时间和严重程度的相关性突出表明，需要快速诊断和适当的免疫治疗，以防止对海马体的持续损害。先进的成像方案可能允许对结构损伤进行更详细的分析，以在临床常规检查中评估疾病进展，并在前瞻性试验中进行治疗评估。
BACKGROUND: The majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis suffer from persistent memory impairment despite unremarkable routine clinical magnetic resonance imaging. With improved acute care in these patients, neurocognitive impairment represents the major contributor to long-term morbidity and has thus become a focus of attention.METHODS: Forty patients with anti-NMDAR encephalitis after the acute disease stage and 25 healthy control subjects underwent multimodal structural imaging that combined volumetry of hippocampal subfields with analysis of hippocampal microstructural integrity. Verbal and visuospatial memory performance was assessed in all patients and correlation and mediation analyses were performed to examine associations between hippocampal structural integrity, memory performance, and disease severity.RESULTS: Hippocampal volumes were significantly reduced in patients and hippocampal subfield analysis revealed bilateral atrophy of the input and output regions of the hippocampal circuit. Microstructural integrity was impaired in both hippocampi in patients. Importantly, hippocampal volumetric and microstructural integrity measures correlated with memory performance and disease severity and duration. Mediation analysis revealed that hippocampal microstructure mediated the effect of disease severity on memory performance.CONCLUSIONS: Data from this largest cohort of anti-NMDAR encephalitis patients that underwent extensive multimodal magnetic resonance imaging demonstrate that structural hippocampal damage and associated memory deficits are important long-term sequelae of the encephalitis. Correlation with disease duration and severity highlights the need for rapid diagnosis and adequate immunotherapy to prevent persistent damage to the hippocampus. Advanced imaging protocols may allow a more detailed analysis of structural damage to assess disease progression in clinical routine examinations and for therapy evaluation in prospective trials.